Fig. 1.

(A) Clinical features include hair thinning, bilateral ptosis, and marked facial diplegia with prominent temporalis muscle wasting, jaw weakness and mild neck flexor and extension weakness. (B) Illustrates a severe mitochondrial histochemical defect, characterized by subsarcolemmal mitochondrial accumulation (ragged-red fibers) on the SDH reaction and in excess of 90% COX-deficient fibers following COX (C) and sequential COX-SDH (D) histochemistry. (E) Sequencing of the mitochondrial genome identified the well-characterised m.8344A > G MTTK gene mutation which was shown to be present at very high levels of heteroplasmy in the patient’s skeletal muscle (94% mutation load) but lower levels in blood and urine by quantitative pyrosequencing. (F) Analysis of samples from the patient’s clinically-unaffected mother (16% mutation load in blood; 18% mutation load in urine) and sister (3% mutation load in blood; 4% mutation load in urine) confirmed lower levels of the m.8344A > G heteroplasmy and maternal transmission, whilst the mutation could not be detected in blood from her clinically-unaffected 14 year-old nephew.